Urine cortisol concentration as a biomarker of stress is unrelated to IVF outcomes in women and men

Purpose

Our primary objective was to assess associations between urine cortisol as a biomarker of psychological stress and in vitro fertilization (IVF) outcomes. A secondary objective was to assess associations between toxic metals and cortisol.

Methods

Urine and blood specimens were collected from 52 women and 28 male partners completing a first IVF procedure, on the day of oocyte retrieval. Urine cortisol was measured with an enzyme-linked immunosorbent assay. Mercury (Hg), cadmium (Cd), and lead (Pb) were determined in blood and Cd in urine by inductively coupled plasma-mass spectrometry.

Results

No associations were indicated for cortisol with IVF outcomes in multivariable regression models adjusted for covariates. However, we detected positive linear associations for cortisol and urine Cd (β = 9.96, 95%CI 1.52, 21.44) and blood Hg (β = 1.44, 95%CI 0.31, 3.18). An exploratory stratified analysis suggested a potential inverse association between urine cortisol and oocyte fertilization among women with low, but not high blood Hg.

Conclusion

While limited, these preliminary data suggest that psychological stress may not play a major role in IVF outcomes, which therefore could be one less concern for couples and their clinicians. Our data also raise the possibility for toxic metals to modify associations between cortisol and IVF outcomes among women. However, these preliminary results require corroboration in an experimental animal model and confirmation in a larger, more definitive observational study.     

The predictive value of anti-mullerian hormone on embryo quality, blastocyst development, and pregnancy rate following in vitro fertilization-embryo transfer (IVF-ET)

Purpose

The objective of this study was to investigate the predictive value of anti-Mullerian hormone (AMH) on fertilization rate (FR), blastocyst development, embryo quality, the outcome of the pregnancy and the live birth rate (LBR) following in vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI).

Method

In this prospective study outcomes were followed in 83 women undergoing cycles of IVF/ICSI within a university hospital. Basal serum AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH) and antral follicle count (AFC) were measured on Day 3. Serum AMH (Gn6 AMH ) level was measured on Day 6 after the administration of gonadotrophin (Gn). AMH was measured in follicle fluid (FF AMH) on the day of ovum pick-up (dOPU). The numbers of retrieved and fertilized oocytes, good quality embryos and blastocysts were counted. Secondary outcome variables included clinical pregnancy rate (CPR) and LBR.

Results

Spearman correlation analysis indicated that the numbers of oocytes, good quality embryos and blastocysts were associated with AMH (P < 0.05) and that LBR was correlated with FF AMH (r = 0.495, P < 0.05). No associations were found between FR and AMH (P > 0.05). Receiver operating characteristic analysis showed that the sensitivity of FF AMH at predicting CPR was 91.2 %; the specificity was 86.5 % and ROC_AUC was 0.893 (P < 0.0001).

Conclusion

AMH parameters were correlated with good quality embryos and blastocysts, but only FF AMH showed a significant correlation with LBR and CPR.     

Does reducing gamete co-incubation time improve clinical outcomes: a retrospective study

Purpose

The objective of this retrospective study was to determine whether patients undergoing in vitro fertilization (IVF) benefit from reducing the gamete co-incubation time.

Methods

Patients (n = 570) were enrolled, including 281 patients in the reduced incubation time group (2-h incubation) and 289 patients in the standard IVF group (18-h incubation).

Results

The observed outcomes, including the clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), and miscarriage rate (MR), were similar between the two groups. When the data were divided into two subgroups based on the maternal age (≤30 and >30 years), the rates of top-quality embryos (30.83 vs. 25.89 %; p = 0.028), CPR (66.67 vs. 42.11 %; p = 0.013), and IR (41.90 vs. 31.25 %, p = 0.019) of the 2-h incubation group were significantly higher in the younger subgroup. However, for older patients, only a lower MR (7.59 vs. 20.83 %; p = 0.019) was achieved. Reducing the time of incubation still improved the CPR (OR = 1.993, 95 % CI 1.141–3.480) and MR (OR = 3.173, 95 % CI 1.013–9.936) in the younger and older subgroups, respectively, after it was adjusted for potential confounders.

Conclusions

Reducing incubation time improves the clinical results of IVF, although the LBR is not statistically different between the 2- and 18-h incubation time groups. And the specific clinical outcomes of reducing incubation time varied between the >30-year-old and the ≤30-year-old.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0618-8) contains supplementary material, which is available to authorized users.     

The Asn680Ser polymorphism of the follicle stimulating hormone receptor gene and ovarian cancer risk: a meta-analysis

Purpose

The purpose of this study was to conduct a meta-analysis to assess the association between FSHR Asn680Ser polymorphism and ovarian cancer susceptibility.

Methods

A literature search was conducted in PubMed, Embase and the China National Knowledge Infrastructure (CNKI) for all relevant studies published up to September 2013. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 % CIs) were calculated to evaluate the association.

Results

Four case–control studies including 474 ovarian cancer cases and 659 controls met the inclusion criteria. The pooled analyses showed that FSHR Asn680Ser polymorphism was associated with the risk of ovarian cancer (Ser vs Asn: OR = 1.295, 95 % CI 1.057–1.498, P = 0.01; Ser/Ser + Asn/Ser vs Asn/Asn: OR = 1.611, 95 % CI 1.027–2.528, P = 0.038). Subgroup analyses by ethnicity (Caucasian and Asian) further revealed significant associations among Asians (Ser vs Asn: OR = 1.386, 95 % CI 1.066–1.802, P = 0.015; Ser/Ser + Asn/Ser vs Asn/Asn: OR = 1.893, 95 % CI 1.329–2.689, P = 0.000) but not Caucasians. There was no obvious risk of publication bias.

Conclusions

The meta-analysis suggests that FSHR Asn680Ser polymorphism may be a risk factor for ovarian cancer in Asians. Due to the limited quantity of the included studies, further studies are needed to validate the above conclusions.     

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin

Purpose

We aimed to characterize the association between levels of serum and follicular fluid (FF) adipocytokines, reflected by the leptin to adiponectin ratio (L:A ratio), and oocyte quality and in vitro embryo development in women undergoing assisted reproduction. We also aimed to assess whether follicular hormonal pathways mediate this interaction.

Methods

We prospectively collected FF from up to four individual preovulatory follicles (n = 76) and fasting sera from women (n = 31) without endocrinopathies undergoing in vitro fertilization (IVF) at a university-based center for assisted reproduction. Leptin, total adiponectin, insulin, insulin-like growth factor 1 (IGF-1), and ovarian steriods were measured using enzyme immunoassay. Oocyte maturity, fertilization, and embryo development were assessed.

Results

FF leptin was similar to serum levels while FF adiponectin was lower. FF leptin (27.10 ± 4.05 ng/mL) and the L:A ratio (11.48E−3 ± 2.57E−3) were related to FF insulin (R² = 0.370 and 0.419, p < 0.001) but not to ovarian steroids or IGF-1, whereas FF adiponectin ( 4.22 ± 0.52 ug/mL) correlated only with leptin (R² = −0.138, p = 0.001). Oocytes from a high FF L:A ratio environment were 81 % (RR 1.81 [95%CI 0.97–3.37]) more likely to undergo successful cleavage and 117 % (RR 2.17 [95 % CI 1.06–4.44]) more likely to obtain viable cleavage morphology compared to a low FF L:A ratio environment, even when adjusted for FF insulin, an independent predictor of cleavage.

Conclusions

Certain adipocytokines, particularly the L:A ratio in the FF of the preovulatory follicle, are related to successful in vitro embryo development. This action may be independent of FF insulin.     

Perceptions among infertile couples of lifestyle behaviors and in vitro fertilization (IVF) success

Purpose

To assess how patients perceive various lifestyle behaviors impact IVF success.

Methods

Cross-sectional study of heterosexual, English-speaking couples (n = 138) who completed web-based surveys during IVF treatment cycle. Perceived impact of lifestyle choices assessed by multivariable logistic regression and p-value tests for linear trend (P_t).

Result(s)

During the IVF cycle, most patients consider it helpful for women to exercise (76 %), avoid stress (87 %) and limit activity after embryo transfer (92 %). The majority of patients (62 %) consider rigorous exercise (4+ h/week) helpful and nearly one-third (32 %) perceive benefit to complete bed rest after transfer. Overall, couples with a sex-specific infertility diagnosis are more likely to consider partner’s lifestyle choices impactful: male-factor couples are more likely to consider it helpful for men to limit cellular phone use (OR:2.73,CI:1.06–7.04) and diminished ovarian reserve couples are more likely to consider it helpful for women to limit exposure to plastics (OR:2.38,CI:1.03–5.51). Patients at higher levels of education (P_t < 0.01) and income (P_t < 0.01) are less likely to consider lifestyle impactful.

Conclusion(s)

Patient perceptions of the impact of lifestyle factors on IVF success vary by sex, infertility diagnosis and socioeconomic factors. Despite counseling to the contrary, many patients perceive benefit to rigorous exercise during the IVF cycle and complete bedrest following transfer. Results provide insight into patient beliefs and highlight opportunities to improve patient education, alleviate patient anxieties and potentially improve IVF outcomes.     

Serum progesterone concentration on day of embryo transfer in donor oocyte cycles

Purpose

To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles.

Methods

Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50–100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50–100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age.

Results

Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60–0.94, p = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60–0.98, p = 0.04), as compared to those with P ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients.

Conclusions

Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.     

Pregnancy with oocytes characterized by narrow perivitelline space and heterogeneous zona pellucida: is intracytoplasmic sperm injection necessary?

Purpose

This retrospective study analyzed fertilization protocols and pregnancy outcomes for oocytes with with narrow perivitelline space and heterogeneous zona pellucid (NPVS/HZP).

Methods

In 63 in-vitro fertilization cycles filled with NPVS/HZP oocytes (abnormal oocytes group) and 521 cycles with normal oocytes (normal oocytes group), major clinical and laboratory parameters were recorded and compared in different fertilization cycles (conventional IVF cycles, rescue ICSI cycles, and traditional ICSI cycles).

Results

NPVS/HZP oocytes meant lower MIIoocytes rates in both IVF and ICSI cycles compared with normal oocytes (p < 0.05). The 2PN rates for abnormal oocytes were significantly lower than those for normal oocytes in both conventional IVF cycles (58.8 % VS 71.3 %, P < 0.05) and rescue ICSI cycles (58.0 % VS 78.0 %, P = 0.0000). The high-quality embryo rates in normal oocytes groups were significantly higher than those in abnormal oocytes groups in different fertilization cycles (52.2 % VS 35.0 %, P < 0.01; 42.9 % VS 23.9 %, P < 0.001; 50.6 % VS 31.0 %, P = 0.0000, respectively). No clinical pregnancy was obtained from abnormal oocytes in 11 conventional IVF cycles. The clinical pregnancy rates in rescue ICSI and traditional ICSI cycles were comparatively lower in abnormal oocytes groups, but there was no significant difference as compared with normal oocytes groups (35.0 % VS 48.1 % and 26.7 % VS 50.7 %, P > 0.05, respectively).

Conclusions

Retrieval of oocytes characterized by NPVS/PZP from cycle to cycle was one of the reasons for obscure infertility. ICSI may be the right way to avoid fertilization failure and get pregnancy in women with NPVS/HZP oocytes.     

Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS

Purpose

The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function.

Methods

Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student’s t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient.

Results

PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02).

Conclusions

Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.     

Impact of elevated peak serum estradiol levels during controlled ovarian hyperstimulation on the birth weight of term singletons from fresh IVF-ET cycles

Purpose

To investigate the impact of elevated serum estradiol (E₂) levels on the day of hCG trigger on the birth weight of term singletons after fresh In Vitro Fertilization (IVF)-Embryo Transfer (ET) cycles.

Methods

Retrospective cohort study of all patients initiating fresh IVF-ET cycles resulting in live births between January 2004 and February 2013. The incidence of low birthweight (LBW) term singletons in patients with E₂ levels on day of hCG trigger above or below the 95 % cutoff for E₂ values in our clinic (3,069.2 pg/mL) was estimated. Multiple gestations and vanishing twin pregnancies were excluded.

Results

Two thousand nine hundred thirty-nine singleton live births were identified for inclusion. One hundred forty seven (5 %) and 2792 (95 %) live singleton births occurred in patients with peak E₂ levels above and below 3,069.2 pg/mL, respectively. The overall incidence of term LBW was 5.4 % in the >3,069.2 pg/mL group compared to 2.4 % in the ≤3,069.2 pg/mL group (P = .038). An E₂ level >3,069.2 pg/mL on the day of hCG administration was associated with increased odds of LBW term singletons (OR = 2.29; 95 % CI = 1.03–5.11). The increased odds remained unchanged when adjusting for maternal age (aOR = 2.29; 95 % CI = 1.02–5.14; P = .037), gestational age at delivery (aOR = 2.04; 95 % CI = 1.22–3.98; P = .025), and day 3 versus blastocyst transfer (aOR = 2.5; 95 % CI = 1.11–5.64; P = .023).

Conclusions

Peak E₂ level >3,069.2 pg/mL is associated with increased odds of LBW term singletons after fresh IVF-ET cycles. Conservative stimulation protocols aiming not to exceed an E₂ level of 3,000 pg/mL may be advantageous for placentation and fetal growth if a fresh transfer is planned.     

Live birth rates using conventional in vitro fertilization compared to intracytoplasmic sperm injection in Bologna poor responders with a single oocyte retrieved

Purpose

To compare reproductive outcomes following conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in poor responders fulfilling the Bologna criteria, with a single oocyte retrieved.

Methods

The present retrospective study included 243 Bologna poor responders with a single oocyte retrieved, who were categorized into three groups, depending on the fertilization method and semen quality (IVF non-male factor-IVF/NMF n = 101; ICSI non-male factor ICSI/NMF n = 50; ICSI male factor-ICSI/MF n = 92).

Results

In IVF/NMF, ICSI/NMF and ICSI/MF similar fertilization rates [65.3, 66, 58.7 %, respectively], proportions of embryo formation [63.4, 60, 53.3 %, respectively], proportions of good quality embryos [54.7, 56.7, 57.1 %, respectively], implantation rates [8.9, 10, 8.2 % respectively] and live birth rates per oocyte retrieval [5.0, 4.0, 3.3 %, respectively] were observed. Degeneration rate of oocytes due to mechanical damage was significantly higher after ICSI in the ICSI/NMF and ICSI/MF groups (8 and 6.5 %, respectively) compared to IVF/NMF (0 %) (p = 0.02).

Conclusions

Conventional IVF and ICSI are associated with similar reproductive outcomes in poor responder patients with a single oocyte retrieved. Therefore, the choice of fertilization method should be based primarily on semen quality, in combination with the patient’s previous history. A randomized controlled trial should be performed to confirm this study’s findings that conventional IVF and ICSI have similar reproductive outcomes in poor responders.     

Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems

Purpose

We aimed to analyse the in vitro fertilization-embryo transfer (IVF-ET) outcomes of the patients with sleep disturbances who were administered melatonin.

Methods

A total of 60 patients with sleep disturbances were divided into two groups. The study group (group A, n = 30) had underwent the IVF-ET with melatonin administration and the control group (group B, n = 30) without melatonin. Sleeping status after melatonin administration and the IVF outcomes were compared between the two groups.

Results

Sleeping status change was not significant (p > 0.05). The mean number of the retrieved oocytes, the mean MII oocyte counts, the G1 embryo ratio were significantly higher in the melatonin administered group (group A) than that the non-administered group (group B); p = 0.0001; p = 0.0001; p < 0.05 respectively.

Conclusion

IVF patients with sleep disorders may benefit from melatonin administration in improving the oocyte and the embryo quality, but the sleeping problem itself may not be fixed.     

Improved pregnancy rates with luteinizing hormone supplementation in patients undergoing ovarian stimulation for IVF

Introduction

Luteinizing hormone (LH) is believed to play a role in follicle maturation during the natural cycle. However, the need for co-treatment with recombinant LH (rLH) for controlled ovarian stimulation is controversial.

Purpose

The primary objective of our study was to determine if pregnancy rates are improved when rLH is used in addition to rFSH for ovarian stimulation. Secondary outcomes were fertilization rate, implantation rate and live birth rate.

Methods

A retrospective cohort study was performed of 1565 IVF or ICSI cycles. Outcomes were compared between ovarian stimulation cycles from 2007 when rLH and rFSH was used (n = 765) to 2006 when rFSH only was used (n-800).

Results

Improved outcomes were found for rLH + rFSH versus rFSH alone for; pregnancy rate (61% and 54% respectively, p = 0.006), live birth rate (49% and 42% respectively, P = 0.01), fertilization rate (74% versus 72% respectively, p = 0.04 and implantation rate (41% versus 37% respectively, p = 0.03).

Conclusions

Our large retrospective cohort study showed an improved pregnancy rate and live birth rate with rLH supplementation. This was associated with an improved fertilization and implantation rate and therefore may reflect an improvement in oocyte quality and/or uterine receptivity.     

Public perspectives on the use of preimplantation genetic diagnosis

Purpose

To study the perspectives of the United States population towards the use of preimplantation genetic diagnosis (PGD) in various clinical scenarios.

Methods

Online cross-sectional population based questionnaire of a nationally representative sample according to age, gender, race/ethnicity, income, education and religion.

Results

A total of 1006 completed the questionnaire with an overall response rate of 94 %. A majority supported PGD for diseases fatal early in life or those causing lifelong disability (72.9 and 66.7 %, respectively); only 48.0 % supported PGD for diseases that manifest late in life. Respondents were more supportive of PGD for genetic diseases if they were aware of PGD prior to the survey (OR = 1.64; CI = 1.13–2.39). However, a small proportion were in favor of genetically-based trait selection: 21.1 % supported PGD for sex selection, 14.6 % for physical traits and 18.9 % for personality traits. Compared to women, men were nearly two- to three-fold more supportive of PGD for sex selection (OR = 1.65; CI = 1.20–2.78), physical traits (OR = 2.38; CI = 1.60–3.48) and personality traits (OR = 2.31; CI = 1.64–3.26). Compared to Caucasians, Asians (OR = 3.87; CI = 1.71–8.78) and African Americans (OR = 1.61; CI = 1.04–2.74) were more supportive of PGD for sex selection.

Conclusions

In a nationally representative sample, a majority supported PGD to identify early onset diseases. We noted significant variation in opinions by sex, race, and education. There was more support among those with prior knowledge of PGD suggesting that education about PGD may foster favorable opinions. This study identifies public knowledge and attitudes that may be used to shape future research hypotheses and clinical policies.     

The role of genetic and autoimmune factors in premature ovarian failure

Purpose

To identify the role of both genetic (number of CGG repeats in the FMR1 gene) and autoimmune factors (anti-ovarian antibodies) in premature ovarian failure (POF).

Methods

In cross-sectional study, 78 women with POF were divided into 3 groups by the number of CGG repeats (less than 28, 28–36, more than 36) in any of the FMR1 gene alleles. We performed the detection of skewed X-chromosome inactivation, CGG repeats in the FMR1 gene, anti-ovarian antibodies (AOA) and sex hormones tests.

Results

Compared to a higher or lower number of CGG repeats the 28–36 triple CGG counts are strongly associated with the AOA detection (RR = 19.23, 95 % CI = 2.63–100.0). The women with autoimmune-driven POF have significantly higher anti-Mullerian hormone levels in comparison to women with non-autoimmune-driven POF.

Conclusion

The presence of AOA above 10 IU/mL is associated with the normal number of CGG repeats in regard to ovarian reserve and a better preservation of follicular primordial pool in the women with POF.     

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

Background and aims

Many epidemiological studies have revealed a positive correlation between medical radiation exposure and the reproductive health in female childhood cancer survivors. However, because of variations in the samples size, such studies showed partly inconsistent conclusions. The aim of this meta-analysis was to clarify the association between radiotherapy and the risk of reproductive health impairment for female who survived from childhood cancer.

Methods

Fourteen cohort studies involving childhood radiotherapy were selected as the exposure of interest and the impaired reproductive health condition during the childbearing age as the outcome. Among meta-analysis of observational studies found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant observational studies which surveyed the association of medical radiation and reproductive health in female childhood cancer survivors. Review Manager 5.2 and STATA 12.0 software were used to perform the meta-analysis. Study-specific estimations for each outcome were combined into a pooled relative risk (RR) with 95 % confidence interval (CI) by a meta-analytic approach.

Results

Based on a random-effects meta-analysis, significant association between infertility (RR = 1.28, 95 % CI = 1.16–1.42), acute ovarian failure (AOF) (RR = 9.51, 95 % CI = 5.03–17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR = 14.79, 95 % CI = 3.36–66.64), stillbirth (RR = 1.19, 95 % CI = 1.02–1.39) and low birth weight (RR = 2.22, 95 % CI = 1.55–3.17) were identified. Conversely, no significant results were found in abortion and congenital malformations.

Conclusions

To the best of our knowledge, this is the first meta-analysis assessing the effect of medical radiation on female childhood cancer survivors’ reproductive capability and pregnancy outcomes. Although there were some limitations, our meta-analysis further supported that radiotherapy was a risk factor for reproductive health problems of female who survived from childhood cancer.     

Reproductive implications of psychological distress for couples undergoing IVF

Objective

To study implications of psychological distress on in vitro fertilization (IVF) outcome of an infertile couple.

Methods

Prospective study in an academic infertility practice setting. Couples undergoing embryo transfer (ET) following IVF were offered participation. Female patient (n = 89) and partner (n = 77) completed questionnaires reflecting dysphoria (POMS) and pessimism (LOT) after undergoing ET. Relationship between dysphoria and pessimism and implications of individual and couple’s psychological distress on IVF cycle parameters and outcomes were assessed using multivariable analyses.

Results

Statistically significant correlations between dysphoria and pessimism were observed within the individual and between partners, (p < 0.01). Higher couple pessimism correlated with longer duration of controlled ovarian hyperstimulation (COH, p = 0.02); higher partner psychological distress related to lower fertilization rate (FR, p = 0.03). On adjusted analyses, partner’s depression score was an independent predictor of reduced likelihood of clinical pregnancy (p = 0.03).

Conclusions

Our data validate the concept of a “stressed couple”. Adverse implications of a couple’s psychological distress for gamete biology (longer duration of COH and lower FR with increasing distress) are suggested. Partner’s depressive scores negatively correlated with IVF success. These findings suggest the importance of including partner’s evaluation in studies that focus on effects of psychological stress on IVF outcome; future studies should examine whether interventions aimed at reducing psychological stress for the infertile couple may improve IVF cycle success.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-013-0098-7) contains supplementary material, which is available to authorized users.     

Prognostic value of growth of 4-cell embryos on the day of transfer in fresh IVF-ET cycles

Purpose

To investigate the prognostic value of growth of 4-cell embryos on the day of transfer in determining clinical pregnancy and live birth rates after fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles.

Methods

Retrospective cohort study of all patients between January 2008 and January 2013 initiating fresh IVF-ET cycles resulting in embryos that were not more than 4 cells 72 h after oocyte retrieval in the morning of their transfer. Patients were stratified into 2 groups based on whether embryos did or did not grow more than the 4-cell stage on the afternoon of ET. The odds of clinical pregnancy and live birth were considered as primary outcomes. Student’s t-tests and Chi-square (χ2) tests were used as inidicated, with logistic regression controlling for maternal age and number of embryos transferred.

Results

Three hundred forty three patients were identified for inclusion: 165 and 178 patients had 4-cell embryos with and without growth on the afternoon of ET, respectively. The demographic and baseline IVF cycle characteristics of the study cohort were comparable. Patients with embryo growth had higher clinical pregnancy (13.9 % vs. 4.49 %) and live birth (10.9 % vs. 3.37 %) rates compared to patients without embryo growth. This represented an overall increased odds of clinical pregnancy [Odds ratio (OR) = 3.44; 95 % Confidence Intervals (CI) 1.49–7.93; P = 0.004)] and live birth (OR = 3.51; 95 % CI 1.36–9.07; P = 0.01). The increased odds remained unchanged after adjusting for maternal age and number of embryos transferred.

Conclusions

Transfer of 4-cell embryos 3 days after oocyte retrieval can result in clinical pregnancies and live births, albeit at a low rate. Growth of an embryo more than the 4-cell stage on the afternoon of ET may serve as a positive prognostic factor for IVF-ET cycle outcome.     

Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience

Purpose

To compare the in-vitro fertilization (IVF) outcomes of cancer patients who underwent oocyte retrieval and embryo/oocyte cryopreservation prior to gonadotoxic therapy to those of age and time-matched controls with tubal factor infertility.

Methods

All cancer patients who underwent embryo/oocyte cryopreservation at our institution from 1997 to 2014 were reviewed. Primary outcomes were total dose of gonadotropins used, number of oocytes retrieved, and number of 2pn embryos obtained. Outcomes were compared to age-matched controls with tubal-factor infertility who underwent a fresh embryo transfer within the same relative time period as the IVF cycle of the cancer patient.

Results

Sixty-three cancer patients underwent 65 IVF cycles, and 21 returned for frozen embryo transfer. One hundred twenty-two age-matched controls underwent IVF cycles with fresh transfer, and 23 returned for frozen embryo transfer. No difference was seen between cancer patients and controls with respect to total ampules of gonadotropin used (38.0 vs. 35.6 respectively; p = 0.28), number of oocytes retrieved (12.4 vs. 10.9 respectively; p = 0.36) and number of 2pn embryos obtained (6.6 vs. 7.1 respectively; p = 0.11). Cumulative pregnancy rate per transfer for cancer patients compared to controls was 37 vs. 43 % respectively (p = 0.49) and cumulative live birth rate per transfer was 30 vs. 32 % respectively (p = 0.85). Cancer patients had a higher likelihood of live birth resulting in twins (44 vs. 14 %; p = 0.035).

Conclusions

Most IVF outcomes appear comparable for cancer patients and age-matched controls. Higher twin pregnancy rates in cancer patients may reflect lack of underlying infertility or need for cancer-specific transfer guidelines.     

Associations between TNF-α and interleukin gene polymorphisms with polycystic ovary syndrome risk: a systematic review and meta-analysis

Background

The associations between TNF-α and Interleukin gene polymorphisms and polycystic ovary syndrome (PCOS) risk have been studied in numerous epidemiological studies, but the results remain controversial. To investigate whether these polymorphisms facilitate susceptibility to PCOS, we conducted a comprehensive systematic review and meta-analysis.

Methods

PubMed, Embase, Web of Science, Medline, CNKI, and Google Scholar were searched to obtain the genetic association studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Odds ratios (OR) with corresponding 95 % confidence intervals (CI) were used to assess the strengths of the associations. Funnel plots and Egger’s tests were performed to test for possible publication bias. All statistical analyses were performed using Review Manager 5.2 and STATA11.0.

Results

Eighteen articles were included in the final meta-analysis. The studies involved the following polymorphisms: TNF-α -308G > A, TNF-α -805C > T, TNF-α -1031 T > C, IL-1A -889C > T, IL-1B -511C > T, IL-1B +3953 T > C, IL-6 -174G > C, IL-10 -819C > T, IL-10 -1082A > G, IL-18 -607C > A, and IL-18 -137G > C. Our results show a significant association between PCOS risk and the TNF-α -1031 T > C polymorphism (For TC + CC vs. TT: OR = 2.09, 95 % CI = 1.58–2.76, p < 0.0001. For C allele vs. T allele: OR = 1.67, 95 % CI = 1.33–2.09, p < 0.0001) and between PCOS risk and the IL-6 -174G > C polymorphism (For CC + GC vs. GG: OR = 0.49, 95 % CI = 0.25–0.95, p = 0.03. For CC vs. GG: OR = 0.48, 95 % CI = 0.28–0.80, p = 0.005. For C vs. G: OR = 0.60, 95 % CI = 0.42–0.87, p = 0.007). No associations were found with the other genetic models.

Conclusion

The results of the meta-analysis suggest positive associations between the TNF-α -1031 T > C and IL-6 -174G > C polymorphisms and the risk of PCOS. No associations are found between PCOS risk and the TNF-α -308G > A, TNF-α -805C > T, IL-1A -889C > T, IL-1B -511C > T, IL-1B +3953C > T, IL-10 -819C > T, IL-10 -1082 A > G, IL-18 -607C > A, and IL-18 -137G > C polymorphisms. However, due to the heterogeneity and low quality of the studies related to PCOS polymorphisms in the meta-analysis, the results should be interpreted with caution. Future multi-ethnicity studies of homogeneous populations of PCOS patients with larger sample sizes and well-matched controls are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s10815-015-0449-7) contains supplementary material, which is available to authorized users.